the Editor Posttraumatic stress disorder (PTSD) is moderately heritable with approximately

Published May 30, 2016

the Editor Posttraumatic stress disorder (PTSD) is moderately heritable with approximately 30 to 40% of the variance associated with the disorder attributable to genetic variance (1). samples of survivors from discord zones in Africa minor allele service providers of two SNPs in (rs10038727 and rs4576167) exhibited a decreased TC-DAPK6 risk of lifetime PTSD over and above the effects of lifetime traumatic weight. We sought to replicate the association between variance in and lifetime PTSD using available genetic data from a sample of the Detroit Neighborhood Health Study (DNHS). The DNHS is a longitudinal epidemiologic study of factors associated with trauma exposure PTSD and other mental disorders in a representative sample of predominantly African American adults from your urban Detroit area [for more details see (7)]. Participants completed a 40-minute interview assessing demographics lifetime exposure to 20 different traumatic events and psychopathology. The PTSD Checklist-Civilian Version (PCL-C) (8) was used to assess PTSD symptoms in reference TC-DAPK6 to the worst traumatic event identified by the participant as well as to a randomly selected event from the remaining events endorsed. Diagnoses of lifetime PTSD were given if Criteria A-F were met with respect to either the worst or the randomly selected event. Participants were also invited to provide whole blood or saliva samples for genotyping. The DNHS was approved by the Institutional Review Table at the University or college of Michigan and TC-DAPK6 all participants provided written informed consent. Of the three SNPs in that have been associated with memory and PTSD (rs17070145 rs10038727 and rs4576167) only one SNP-rs10038727-was genotyped in CD333 the DNHS. A total of 598 participants (57% female 83 African American mean age = 52.3 years = 16.1 years range = 18-95) provided information regarding trauma exposure and PTSD and had valid data for rs10038727. rs10038727 minor (A) allele frequency was 0.19 and genotype frequencies were as follows: A/A (= 20 3.3%) A/G (= 186 31.1%) and G/G (= 392 65.6%). Genotype frequencies did not deviate significantly from Hardy-Weinberg equilibrium = .79. A logistic regression analysis predicting lifetime PTSD status was conducted with sex age and lifetime traumatic weight (calculated by summing the number of traumatic event types endorsed) joined as covariates. The first two principal components from a TC-DAPK6 multidimensional scaling analysis of genome-wide data were also included as covariates to TC-DAPK6 adjust for populace stratification. Results revealed that the rs10038727 SNP (coded additively) significantly predicted lifetime PTSD status with the minor (A) allele associated with a reduced risk of PTSD odds ratio (OR) = 0.64 [95% confidence interval (CI) = 0.406-0.997] = .049. Greater traumatic weight was additionally associated with a greater risk of lifetime PTSD OR = 1.23 [95% CI = 1.155-1.304] < .0001. Consistent with Wilker et al. (6) we did not find evidence of a significant conversation between rs10038727 genotype and lifetime traumatic weight in predicting lifetime PTSD status = .56. Additionally lifetime traumatic weight and rs10038727 genotype were not correlated = ?0.02 = .68. Results of the current study provide impartial replication of a relationship between rs10038727 in and reduced risk of lifetime PTSD. Whereas Wilker et al. (6) originally recognized this association in African samples of survivors from discord zones our results extend this obtaining to a predominantly African American sample of individuals residing in neighborhoods with high rates of trauma exposure in urban Detroit. Although there is some indirect evidence suggesting that rs10038727 may play a regulatory role given its location in an intronic region with high transcription factor binding affinity (6) direct investigations of molecular processes that underlie the association between this SNP and PTSD are needed. KIBRA has been postulated to influence synaptic plasticity and long-term potentiation by interacting with different binding partners (e.g. protein kinase Mζ dendrin) (9 10 and it is of interest for future research to examine whether rs10038727 may impact these processes. Further research should also investigate the additional SNPs in that have been associated with memory and PTSD given that only rs10038727 was genotyped in the DNHS. Nevertheless our current.